Dupilumab, a Potential Novel Treatment for Hailey-Hailey Disease.

Abstract

Background/Objectives: Hailey-Hailey disease (HHD) is an uncommon genodermatosis with autosomal dominant inheritance caused by loss-of-function mutations in the ATP2C1 gene, which lead to disruption in keratinocyte adhesion and intraepidermal acantholysis. The chronic nature of the disease, its frequent recurrences and the lack of specific treatment pose real challenges in the long-term management of these patients. Recent studies have evaluated the effect of dupilumab, a human monoclonal antibody that blocks interleukin-4 and -13 receptor in refractory HHD, with very promising results. The aim of this study was to review the published data on the use of dupilumab for the treatment of HHD, to present our own experience in the field, and to discuss the mechanisms underlying dupilumab's beneficial effects in HHD and the future treatment perspectives. Methods: A search of the medical literature on the use of dupilumab in the treatment of HHD was conducted. The terms "Hailey-Hailey disease", "benign familial pemphigus", "benign chronic pemphigus", and "dupilumab" were searched across multiple databases (Medline, Chrocane Library, EMBASE) from inception until 30 September 2024. Results: To date, six manuscripts describing 11 refractory HHD cases treated with dupilumab have been published. All the patients experienced significant clinical improvement. The authors reported sustained disease quiescence in seven patients (64%), monitored for 5 to 24 months. None of the patients experienced adverse effects related to dupilumab. To the existing evidence, we add a new case of recalcitrant HHD successfully treated with dupilumab. Conclusions: Mounting evidence indicates dupilumab as a safe and efficient therapeutic alternative in patients with severe, refractory HHD. However, the long-term efficacy of dupilumab and the optimal therapeutic regimen for HHD are yet to be determined.